Molecular mechanisms of invadopodium formation
| Autor: | Corina Sarmiento, Tadaomi Takenawa, Salvatore J. Coniglio, Marc Symons, John S. Condeelis, Robert J. Eddy, Hideki Yamaguchi, Jeffrey E. Segall, Mike Lorenz, Hiroaki Miki, Stephan J. Kempiak |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Podosome
Invadopodium Arp2/3 complex Wiskott-Aldrich Syndrome Protein Neuronal Nerve Tissue Proteins macromolecular substances Transfection Models Biological Article Epidermal growth factor Cell Movement Cell Line Tumor Animals Neoplasm Invasiveness Enzyme Inhibitors RNA Small Interfering cdc42 GTP-Binding Protein Research Articles Adaptor Proteins Signal Transducing GRB2 Adaptor Protein Oncogene Proteins biology Epidermal Growth Factor Wiskott–Aldrich syndrome protein Microfilament Proteins Cell Biology Cofilin Tyrphostins Actins Cell biology Extracellular Matrix Fibronectins Rats Wiskott-Aldrich Syndrome Protein Family ErbB Receptors Cytoskeletal Proteins Cdc42 GTP-Binding Protein Actin Depolymerizing Factors Microscopy Fluorescence Actin-Related Protein 3 Invadopodia Actin-Related Protein 2 biology.protein Quinazolines Cell Surface Extensions Carrier Proteins |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Invadopodia are actin-rich membrane protrusions with a matrix degradation activity formed by invasive cancer cells. We have studied the molecular mechanisms of invadopodium formation in metastatic carcinoma cells. Epidermal growth factor (EGF) receptor kinase inhibitors blocked invadopodium formation in the presence of serum, and EGF stimulation of serum-starved cells induced invadopodium formation. RNA interference and dominant-negative mutant expression analyses revealed that neural WASP (N-WASP), Arp2/3 complex, and their upstream regulators, Nck1, Cdc42, and WIP, are necessary for invadopodium formation. Time-lapse analysis revealed that invadopodia are formed de novo at the cell periphery and their lifetime varies from minutes to several hours. Invadopodia with short lifetimes are motile, whereas long-lived invadopodia tend to be stationary. Interestingly, suppression of cofilin expression by RNA interference inhibited the formation of long-lived invadopodia, resulting in formation of only short-lived invadopodia with less matrix degradation activity. These results indicate that EGF receptor signaling regulates invadopodium formation through the N-WASP–Arp2/3 pathway and cofilin is necessary for the stabilization and maturation of invadopodia. |
| Databáze: | OpenAIRE |
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